Because cancer is the second leading cause of death in postmenopausal women, detailed investigations are warranted to identify potentially modifiable risk factors. The Iowa Women's Health Study recruited a population-based cohort of 41 ,837 Iowa women, aged 55-69 years in 1986, to determine prospectively whether body fat distribution, diet, and other factors were related to cancer incidence. Exposure and lifestyle information was collected in a baseline mailed survey and three followup surveys. Cancer incidence and mortality have been ascertained since 1986 by linkage with the Iowa Health (SEER) Registry and National Death Index. Results to date, summarized in over 50 publications, document, for example, associations of an increased waist-to-hip ratio with greater breast cancer incidence and total mortality; associations of increased dietary fat intake with poorer survival, but not greater incidence, of breast cancer; a positive interaction between family history of breast cancer and greater waist-to-hip ratio on breast cancer incidence; associations of increased intake of fruits and vegetables, calcium, and Vitamins E and D with lower colon cancer incidence; associations of a history of transfusion with greater incidence of non-Hodgkin' s lymphoma and kidney cancer; associations of increased intake of fruits and vegetables with lower lung cancer incidence; a possible Mendelian codominant inheritance of an allele that is associated with late onset breast cancer; and certain families with breast cancer having linkage to the BRCA 1 gene. Because of the existing wealth of information on this large cohort of women, we propose in this 5 year renewal to extend follow-up for cancer incidence and mortality through 13 years. We also propose to conduct a mailed survey in 1997 to update exposure and disease information on the women. Further follow-up will allow us to verify earlier results and test hypotheses of diet and fat distribution in relation to rarer neoplasms, such as cancers of the ovary and upper gastrointestinal system. We further propose three new aims: 1) a linkage analysis of 35 families with multiple cases of breast cancer or breast/ovarian/prostate cancer, to explore evidence for inherited susceptibility, 2) a survey of sisters to collect blood for hormonal analyses that may explain the interaction observed between family history of breast cancer and waist-to-hip ratio on the risk of breast cancer, and 3) an evaluation, using existing databases, of whether drinking water contaminants are associated with increased cancer incidence. The proposed project will provide new information on the risk of cancer in older women. This information could be valuable in the primary prevention of this major public health problem.